The use of molecular imaging in basic research, while not a new technique, has shown important growth with the advent of molecular biology techniques and the outcome of various genome sequencing projects. This technology may have a significant impact on clinical care in the future, as it has the potential for applications in the diagnosis of diseases such as neurological diseases, cardiovascular diseases and cancer.
The development of probes, or molecular imaging agents, that specifically seek out targets in living organisms is one of the key fundamentals in this area of research. Genomics and proteomics research has already uncovered many new potential targets. Imaging agents against these new targets will not only help understand their roles in disease progression, but will also aid in the generation and assessment of new therapeutics. The probes generally comprise a targeting moiety, which allows the probe to home in on the target molecule, and an imaging moiety, which allows for detection of the probe.
Ideally, a molecular imaging agent should have appropriate affinity, specificity, and metabolic stability, such that it homes in on its target with sufficient concentration and retention time in order to be detectable in vivo. Ideally, it should also have a relatively short half-life in the circulation, and display very low non-specific binding. Many types of imaging moieties have been used in molecular imaging; for example, radiolabels, fluorophores, and Near Infra-Red (NIR) fluorochromes. Targeting moieties have included monoclonal antibodies, lipoproteins, and polypeptides. These and other types of targeting moieties have been utilized to generate optical probes, which have been used by many investigators for the optical imaging of different types of tumors (Wagnières et al., 1998; Rosenthal et al., 2007; McCormack et al., 2007; Peng et al., 2008). One advantage of NIR probes is their capacity for imaging of deeper tissues due to their properties of high penetration, low tissue absorption and scattering.
In post-genomics biotechnology and drug discovery research, there is a great interest in developing peptide-based molecules that home to new targets as the next generation of more versatile targeting moieties. Peptide-based targeting moieties typically show lower affinity for their target than monoclonal antibodies. However, whereas antibodies have limitations that are linked to poor diffusion and target accessibility, peptides have advantages such as small size (which implies good tissue penetration), easy synthesis and a faster clearance rate from the circulation (which can lead to good contrast). To date, the identification of effective peptide-based targeting moieties has been focused primarily on peptides that interact with vascular targets.
Of particular interest within the molecular imaging field is its potential as a tool for diagnosing cancers and assessing response to treatment. Carcinomas are the most common human malignancy, and arise from epithelial cells. Progression of epithelial cancers begins with the disruption of cell-cell contacts as well as the acquisition of a migratory (mesenchymal-like) phenotype. This phenomenon, which is called an epithelial-to-mesenchymal transition (EMT), is considered to be a crucial event in late stage tumor progression and metastasis (Gupta and Massague, 2006; Berx et al., 2007). One of the key players in EMT is the secreted protein TGF-β, which suppresses tumor growth initially largely due to its growth inhibitory action on tumor cells of epithelial origin, then at later stages promotes tumor cell progression and metastasis (Massague, 2008). One mechanism by which TGF-β can promote tumor progression is through the induction of an EMT.
The development of improved imaging probes that target the molecular mechanisms associated with tumor formation and progression would be beneficial in the diagnosis and ongoing assessment of cancer, and possibly in the development and assessment of therapeutics.